title: β-Lapachone: a naphthoquinone with promising antischistosomal properties in mice.
abstract: The activity of β-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione, β-lap) against different stages of Schistosoma mansoni was investigated in mice. Mice infected with 50 cercariae (BH strain) were intraperitoneally treated at a dose of 50 mg/kg for 5 consecutive days, starting on the 1st, 14th, 28th and 45th days after infection, to evaluate the effect of β-lap on skin schistosomula, lung schistosomula, young worms (before oviposition) and adult worms (after oviposition), respectively. All animals were euthanized 60 days after infection. β-Lap significantly reduced (p<0.001) the number of worms in 29.78%, 37.2%, 24.2% and 40.22% when administered during the phases of skin schistosomula, lung schistosomula, young worms and adult worms, respectively. Significant reduction was also achieved in terms of female burden. In all groups, there was significant reduction in the number of eggs and granulomas in the hepatic tissue. When the intervention was performed during the phase of adult worms, β-lap reduced the size of hepatic granulomas and changed the oogram pattern, lowering the percentage of immature eggs and increasing the percentage of mature and dead eggs. Our data indicate that β-lap has moderate antischistosomal properties. Its molecule may also be used as a prototype for synthesis of new naphthoquinone derivatives with potential schistosomicidal properties. Further studies with different formulations containing β-lap are needed to clearly establish the best dose and route of administration and its mechanism of action against schistosomes.
authors.affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil; Centro de Ciências da Saúde - Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: André de Lima
authors.initials: Ade L
authors.lastname: Aires
authors.affiliation: Centro de Ciências Biológicas - Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Eulália Camelo Pessoa Azevedo
authors.initials: EC
authors.lastname: Ximenes
authors.affiliation: Centro de Ciências Biológicas - Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Vanessa Xavier
authors.initials: VX
authors.lastname: Barbosa
authors.affiliation: Centro de Ciências Biológicas - Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Alexandre José da Silva
authors.initials: AJ
authors.lastname: Góes
authors.affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
authors.forename: Valdênia Maria Oliveira
authors.initials: VM
authors.lastname: Souza
authors.affiliation: Laboratório de Imunopatologia Keizo Asami (LIKA), Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil; Centro de Ciências da Saúde - Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil. Electronic address: jcmonica@globo.com.
authors.forename: Mônica Camelo Pessôa de Azevedo
authors.initials: MC
authors.lastname: Albuquerque
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006099:Granuloma; D008018:Life Cycle Stages; D008099:Liver / Q000469:parasitology; D008107:Liver Diseases / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008168:Lung / Q000469:parasitology; D008171:Lung Diseases / Q000188:drug therapy* / Q000469:parasitology; D019684:Magnoliopsida / Q000737:chemistry; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000254:growth & development; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D012867:Skin / Q000469:parasitology; D012871:Skin Diseases / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D000977:Antiparasitic Agents; D009285:Naphthoquinones; D010936:Plant Extracts; C014638:beta-lapachone
keywords: Granuloma; In vivo; Schistosoma mansoni; Schistosomicidal; β-Lapachone